Arginase as a Potential Biomarker of Disease Progression: A Molecular Imaging Perspective

• Published in: International journal of molecular sciences Vol. 21; no. 15; p. 5291
• Main Authors: S. Clemente, Gonçalo, van Waarde, Aren, F. Antunes, Inês, Dömling, Alexander, H. Elsinga, Philip
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 25.07.2020; MDPI
• Subjects: Amino acids; Animals; Arginase - metabolism; Biomarkers, Tumor - metabolism; Biosynthesis; Carbon; Cardiovascular Diseases - enzymology; Cell growth; Enzymes; Growth factors; Humans; Hydrogen bonds; Immune System Diseases - enzymology; Kinases; Ligands; Mammals; Neoplasm Proteins - metabolism; Neoplasms - enzymology; Neurodegenerative Diseases - enzymology; Nitric oxide; Nitric Oxide Synthase - metabolism; Phosphorylation; Physiology; Polyamines; Regulation; Review; Smooth muscle; Tumor necrosis factor-TNF; nitric oxide; molecular imaging; arginase inhibitors; positron emission tomography (PET); arginase
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms21155291

Arginase is a widely known enzyme of the urea cycle that catalyzes the hydrolysis of L-arginine to L-ornithine and urea. The action of arginase goes beyond the boundaries of hepatic ureogenic function, being widespread through most tissues. Two arginase isoforms coexist, the type I (Arg1) predominantly expressed in the liver and the type II (Arg2) expressed throughout extrahepatic tissues. By producing L-ornithine while competing with nitric oxide synthase (NOS) for the same substrate (L-arginine), arginase can influence the endogenous levels of polyamines, proline, and NO•. Several pathophysiological processes may deregulate arginase/NOS balance, disturbing the homeostasis and functionality of the organism. Upregulated arginase expression is associated with several pathological processes that can range from cardiovascular, immune-mediated, and tumorigenic conditions to neurodegenerative disorders. Thus, arginase is a potential biomarker of disease progression and severity and has recently been the subject of research studies regarding the therapeutic efficacy of arginase inhibitors. This review gives a comprehensive overview of the pathophysiological role of arginase and the current state of development of arginase inhibitors, discussing the potential of arginase as a molecular imaging biomarker and stimulating the development of novel specific and high-affinity arginase imaging probes.